Establishment and characterization of patient-derived high-grade glioma cell lines, and validation of their tumorigenicity in murine xenograft model
Background: Diffuse high-grade gliomas (HGGs) include the most aggressive types of brain tumors. Despite current treatment options, which include a combination of surgery, radiotherapy, and chemotherapy, the prognosis remains catastrophic. Patients diagnosed with glioblastoma (GB), the most aggressive HGG, have a median survival of <2 years. Cancer cell lines represent an essential tool in cancer research. Once established, these cells can be used to investigate tumor biology and conduct drug screening trials, contributing to the development of new therapeutic options for patients with glioma.
Aim: The aim of the study was to establish and characterize three new HGG cell lines obtained from different patients and validate their tumorigenicity in a murine xenograft model.
Methods: The three tissue samples were immunohistochemically and molecularly classified as astrocytoma IDH-mutant, Grade 3 (C03); GB IDH-wildtype, grade 4 (N07); and astrocytoma IDHmutant, Grade 3 (L09). These were cultured until the tenth passage for culture establishment. Cell morphology was accessed by light microscopy and phalloidin labeling. To characterize the cell lines, GFAP labeling was performed. Xenograft murine models were used to investigate whether the cell lines retained their tumor-forming ability. Cells from murine tumors were recultured, and morphological evaluation was performed by histopathological analysis.
Results: The three HGG lines were successfully established, and GFAP positivity confirmed their astrocytic origin. Morphologically, the cells presented a fusiform or polygonal shape, with accelerated growth throughout the passages. All three cell lines developed tumors after induction of the xenograft model, and the subculture of these tumors revealed a morphology similar to that of the three cell lines before implantation. Histopathological analysis of the xenograft tumors confirmed the disordered tissue formation commonly found in diffuse gliomas.
Conclusion: The successful establishment of these cell lines and the creation of a biobank will facilitate studies in drug development and glioma tumorigenesis.
Relevance for Patients: The established cell lines will be utilized in assays to analyze glioma tumorigenesis and in screening for novel drug candidates, contributing to the development of new treatments for these patients.
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